Transcranial direct current stimulation (tDCS) over the left Inferior Frontal Gyrus (IFG) was found to improve apraxia of speech (AOS) in post-stroke aphasia, speech fluency in adults who stutter, naming and spelling in primary progressive (PPA). This paper aims to determine whether tDCS over the left IFG coupled with AOS therapy improves speech fluency in patients with PPA more than sham. Eight patients with non-fluent PPA with AOS symptoms received either active or sham tDCS, along with speech therapy for 15 weekday sessions. Speech therapy consisted of repetition of increasing syllable-length words. Evaluations took place before, immediately after, and two months post-intervention. Words were segmented into vowels and consonants and the duration of each vowel and consonant was measured. Segmental duration was significantly shorter after tDCS than sham for both consonants and vowels. tDCS gains generalized to untrained words. The effects of tDCS sustained over two months post-treatment in trained words. Taken together, these results demonstrate that the tDCS over the left IFG facilitates speech production by reducing segmental duration. The results provide preliminary evidence that tDCS can maximize efficacy of speech therapy in non-fluent PPA with AOS.

The oviparous blow fly Calliphora vicina has shown potential as a managed pollination species to support honeybee (Apis mellifera) usage in Australian horticulture. This blow fly species lays eggs onto carrion soon after death and the resultant larvae that hatch are necrophagous and feed on the decomposing tissues of the dead animal. Newly hatched larvae of this fly were provided with plant-based meals (soya bean and canola) and compared with animal-derived meatmeal to determine if plant-based meal could be used to mass rear this blow fly species. Both soyabean and canola meal media did not support the survival of any larvae through to adult eclosion. The addition of only 10% whole egg powder to the plant-based meals enabled survival to eclosion of 39% and 13% on soyabean and canola based medias respectively compared with 76% on animal-based meatmeal with 10% whole egg powder. Larvae fed livestock meatmeal with 10% whole dried egg powder had the fastest development to the pupal stage, the highest pupation rate, the heaviest pupae and the highest subsequent adult eclosion. This study concluded that the use of plant-based meals in the mass rearing of the blow fly C. vicina was neither viable, nor economically viable.

Immunotherapy, particularly Immune Checkpoint Blockade (ICB), has demonstrated significant efficacy in treating melanoma in recent years. However, accurately predicting treatment success and avoiding ineffective therapies remains an unresolved challenge. Therefore, this study aims to develop statistical models utilizing neural networks to forecast the effectiveness of immune checkpoint therapies for melanoma patients. Our models primarily rely on Artificial Neural Networks (ANN) to anticipate both Overall Survival (OS) and Progression-Free Survival (PFS) among melanoma patients undergoing anti-CTLA4 and anti-PD1/anti-PDL1 therapy. We incorporate gene expression data, measured in Transcripts per Million (TPM), derived from bulk tumor RNA-sequencing datasets. Additionally, clinical variables such as gender, age, and treatment type are factored into our analysis. The ANN underwent optimization to attain the highest feasible precision in anticipating the predetermined survival outcome. Issues stemming from high-dimensional data, such as overfitting, were tackled through regularization and feature selection methods. Consequently, the ANN-based model incorporating feature selection exhibited the capacity to forecast survival (PFS) in response to ICB therapy with a maximal precision of 86%. Conversely, the ANN lacking feature selection but incorporating regularization achieved accuracies of up to 72% for PFS and 71% for OS, correspondingly. In order to confront the challenge posed by limited patient samples and to assess replicability, the model underwent training and validation based on the amalgamation of all five datasets. However, this amalgamation failed to enhance predictive performance, necessitating further investigations.

In this study, we aim to explore whether rephrasing enhances the performance of advanced question answering systems in terms of accuracy. Initially, we analyze the effectiveness of Bidirectional Encoder Representations from Transformers (BERT)—a widely used pre-trained language model—when presented with rephrased questions and documents containing distracting details. Our findings reveal that BERT exhibits excessive sensitivity to such instances, prompting us to investigate potential strategies for mitigating this sensitivity. To address the observed decline in performance, we propose a refinement approach for BERT, incorporating techniques such as data augmentation and multitask learning. Specifically, given a question and its context, we generate a series of paraphrases through back-translation. Alongside minimizing the loss between the predicted answer distributions for the original questions—we also minimize the supervised loss associated with the augmented questions. Furthermore, we introduce an auxiliary objective aimed at minimizing the unsupervised loss between the answer distributions of the original and augmented questions. Notably, this auxiliary loss is unsupervised, as it does not directly rely on labels corresponding to the augmented examples. To compute this unsupervised loss, we employ measures such as symmetric Kullback-Leibler divergence and the Jensen-Shannon distance, serving as regularization techniques for the model. The findings revealed that the supervised model exhibited superior performance compared to both the original and our proposed model. However, our proposed model demonstrated a nearly 2% enhancement in both Exact Match (EM) and F1 scores when tested on a paraphrased development set that we formulated. This suggests the potential effectiveness of our proposed approach in enhancing model accuracy and performance.

This study, which was supported by a quantitative research paradigm with two experiment and two control groups of 4x4 quasi-experimental design, aimed to find out the impact of a sustainable progressive STEAM (SP-STEAM Model) application model on 5th grade primary school students critical thinking dispositions and mathematic achievements in Northern Cyprus. The treatment model was applied to experimental groups for 14 weeks of time. Split-plot multiple group analysis of variance (Split-plot ANOVA) statistical technique was used to calculate between and within group significances regarding exogenous variable. SPSS24 software package was used for the analysis. Pre-test and post-test results derived from experiment and control groups revealed significant effect of SP-STEAM Model on 5th grade primary school students’ critical thinking dispositions as measured with CCTDI and mathematic achievements as measured with a dedicated ex-am. The results were discussed in detail under the light of related literature and suggestions for further studies were proposed.

Despite the relative scarcity of studies focusing on pharmacotherapy in aphasia, there is evidence in the literature indicating that remediation of language disorders via pharmaceutical agents could be a promising aphasia treatment option. Among the various agents used to treat chronic aphasic deficits, cholinergic drugs have provided interesting results. In the current review, we focused on published reports investigating the impact of acetylcholine on language and further cognitive disturbances. It has been suggested that acetylcholine plays an important role in neuroplasticity and is related to several aspects of cognition, such as memory and attention. Moreover, cholinergic input is diffused to a wide network of cortical areas, which have been associated with language sub-processes. This could be a possible explanation for the positive reported outcomes of cholinergic drugs in aphasia recovery, and specifically in distinct language processes, such as naming and comprehension, as well as overall communication competence. However, evidence with regard to functional alterations in specific brain areas after pharmacotherapy is rather limited. Finally, despite the positive results derived from the relevant studies, cholinergic pharmacotherapy treatment in post-stroke aphasia has not been widely implemented. The present review aims to provide an overview of the existing literature in cholinergic pharmacotherapy interventions in post-stroke aphasia, following an integrated approach by converging evidence from neuroanatomy, neurophysiology, and neuropsychology.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Additive Manufacturing (AM) provides an opportunity to fundamentally redesign components previously limited by conventional manufacturing techniques. A new process for this workflow of design, manufacture by Powder Bed Fusion (PBF) and validation is presented, to which a case study of a crank for a high performance racing bicycle is applied. Topology optimisation generated conceptually ideal geometry from which a functional design was interpreted. Design for AM considerations were employed to reduce build time, material usage and post-processing labour. PBF was employed to manufacture the parts, and the build quality assessed using Computed Tomography (CT). Static and dynamic functional testing was performed and compared to a Finite Element Analysis (FEA). CT confirmed good build quality of tall, complex geometry with no significant geometrical deviation from CAD over 0.5 mm. Static testing proved performance close to current market leaders, although failure under fatigue occurred after just 2495 ± 125 cycles, the failure mechanism was consistent in both its form and location. These physical results were representative of those simulated, thus validating the FEA. This research demonstrates a complete workflow from design, manufacture, post-treatment and validation of a highly loaded PBF manufactured component, offering practitioners with a validated approach to the application of PBF.

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p<0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p<0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p<0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p<0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol <40 mg/dL in men or <50 mg/dL in women (OR = 1.70); (p<0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

We aimed to reveal the disease burden of aphasia after acute ischemic stroke (AIS) at the national level and investigate the impact of aphasia on tertiary care resources and patient outcomes. The local database from the Cluj-Napoca Emergency County Hospital (CNECH), the second largest stroke center in Romania was used to export demographics, baseline clinical and laboratory data, inpatient length of stay (LOS), NIH Stroke Scale (NIHSS), and discharge modified Rankin Scale (mRS) score data for all AIS patients admitted during March 2019. Of 92 patients included in the study, 30 (32.6 %) had aphasia on admission. In a marginally significant unadjusted hierarchical multiple regression model, individuals with aphasia had a LOS of 1.86 days longer than stroke survivors without aphasia. In an adjusted version of the model, the NIHSS score at baseline was a significant predictor for LOS. In addition, the presence of aphasia was associated with a 1.49 increase in the mean mRS score. Aphasia was a marginally significant predictor for increased LOS. Presence of aphasia was more likely to produce a poor functional outcome. Considering an estimated impact of approximately EUR 3 million on direct medical expenditure annually, future policymaking efforts should improve prevention of stroke and improved access to post-stroke aphasia care in Romania.

We present a case of serious and progressive neuropathy shortly following administration of the herpes zoster subunit (HZ/su) vaccine. The progressive neuropathy occurred a week following the vaccination and progressed until discharge 16 days post admittance. Mild patient’s symptoms persist. The development of neuropathy following HZ/su is exceedingly rare, with an attributable risk of 3 cases per million vaccines administered. A black box warning was issued for this indication, although diagnosis and treatment were not confirmed for this patient. Reporting cases like this is crucial for a comprehensive understanding of vaccine risks and to characterize the underlying etiology of these serious adverse events.

Persons with stroke-induced aphasia (PWAs) are often impaired in tense/time reference (TR) production. It is not clear, however, whether PWAs’ impaired TR production is due to TR-related encoding or retrieval deficits. This study aims at disentangling TR-related encoding deficits from TR-related retrieval deficits in aphasia. Two sentence completion tasks (SCTs) tapping production of past and future reference were administered to eight Greek-speaking PWAs, eight Russian-speaking PWAs, six Italian-speaking PWAs, seven English-speaking PWAs and four groups of language-, age- and education-matched healthy controls. SCT 1 tapped TR-related encoding processes and TR-related retrieval processes to a similar extent. SCT 2 predominantly tapped TR-related retrieval processes. All four control groups performed at ceiling. Three Greek-speaking PWAs, one Russian-speaking PWA, three Italian-speaking PWAs and two English-speaking PWAs showed between-task dissociations. A double dissociation emerged, as some Greek-, Russian- and English-speaking PWAs performed better on SCT 1 than on SCT 2, whereas other Greek- and Italian-speaking PWAs performed worse on SCT 1 than on SCT 2. It will be shown that the experimental design employed here has the potential to disentangle TR-related encoding deficits from TR-related retrieval deficits, as both PWAs with selective TR-related encoding deficits and PWAs with selective TR-related retrieval deficits were identified.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

(1) Background: Several chronic respiratory diseases could be a risk factor for acquiring SARS-CoV-2 infection: among them, Primary Ciliary Dyskinesia (PCD) is a rare (about 1:10.000) inherited ciliopathy (MIM 242650) characterized by recurrent upper and lower respiratory tract infections due to a dysfunctioning of the respiratory cilia; We aimed to investigate if some polymorphisms of the TAS2R38 bitter taste receptor correlate with an increased prevalence of SARS-CoV-2 infection and severity of symptoms in a cohort of PCD subjects; (2) Methods: Patients answered several questions about possible SARS-CoV-2 infection, experienced symptoms and vaccinations; in case of infection, they also filled out a SNOT-22 and ARTIQ questionnaires; (3) Results: Forty PCD adult patients (mean age 36.6 ± 16.7 years, 23 females) participated to the study, out of which 30 % had tested positive for COVID-19 during the last four years; most of them reported a mildly symptomatic disease. We found no differences in age or sex, but a statistic significant difference (p=0.03) was observed in body mass index (BMI), that was higher in the COVID-acquired group (23.2 ± 3.3 vs 20.1 ± 4.1 kg/m2). Genotyping for TAS2R38 polymorphisms showed a prevalence of 28.6% PAV/PAV, 48.6% PAV/AVI and 22.8% AVI/AVI individuals in our cohort. In contrast to our hypothesis, we did not observe a protective role of PAV allele towards SARS-CoV-2 infection; (4) Conclusions: Our findings suggest that subjects with PCD may not be at increased risk of severe outcomes from COVID-19 and the TAS2R38 bitter taste receptor genotype type does not affect SARS-CoV-2 infection.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p>0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

MRI shows in-vivo the three archetypal patterns of CNS volume loss underlying progressive ataxias, namely spinal atrophy (SA), cortical cerebellar atrophy (CCA) and olivopontocerebellar atrophy (OPCA). The MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. A CNS atrophy pattern was identified in 91 conditions: SA in Freidreich’s ataxia, CCA in 5 acquired and 72 (24 dominant, 47 recessive,1 X-linked) inherited ataxias, OPCA in Multi-System Atrophy and 12 (9 dominant, 2 recessive,1 X-linked) inherited ataxias. The MRI-based CNS atrophy pattern may be useful for genetic assessment, identification of shared cellular targets, and repurposing therapies or enlargement of drugs indications in progressive ataxias.

(1) Background: The CEECCA questionnaire assesses the ability to communicate among individuals with aphasia. It was designed using the NANDA-I and NOC standardised nursing languages (SNLs), reaching high content validity index and representativeness index values. The questionnaire was pilot-tested, demonstrating its feasibility for use by nurses in any healthcare setting. This study aims to identify the psychometric properties of this instrument. (2) Methods: 47 individuals with aphasia recruited from primary and specialist care facilities. The instrument was tested for construct validity and criterion validity, reliability, internal consistency, and responsiveness. The NANDA-I and NOC SNLs and the Boston test were used for criterion validity testing. (3) Results: 5 language dimensions explain 78.6% of the total variance. Convergent criterion validity tests showed concordances of up to 94% (Cohen’s κ: 0.9; p<0.001) using the Boston test, concordances of up to 81% using DCs of NANDA-I diagnoses (Cohen’s κ: 0.6; p<0.001), and concordances of up to 96% (Cohen’s κ: 0.9; p<0.001) using NOC indicators. Internal consistency (Cronbach’s alpha) was 0.98. Reliability tests revealed test-retest concordances of 76%-100% (p<0,001). (4) Conclusions: The CEECCA is an easy-to-use, valid, reliable instrument to assess the ability to communicate among individuals with aphasia.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

We present a case report of a young patient with pectus carinatum who experienced a small right apex pneumothorax and exhibited Brugada patterns on electrocardiogram tracing. This is the first clinical case reporting Brugada pattern presentation in both a patient with pectus carinatum and a small pneumothorax. We conducted a clinical, anatomical, and electrocardiographic analysis to explore a physiopathological explanation for these findings, considering our patient had no history or clinical signs of Brugada Syndrome. We conclude that: 1. Pectus carinatum may create a window that facilitates the less resistive measurement of cardiac action potentials; 2. Small pneumothoraces can induce modifications in the cardiac electrical signal detected by surface electrodes, and pectus carinatum could unmask these modifications; and 3. Surface electrodes may measure subepicardial potentials that include and are modified by adjacent pericardial tissues, potentially resulting in alterations in transmural potential differences, thus producing fictitious Brugada patterns. Similarly, there is a possibility that the right ventricular outflow tract may be included within the subendocardial potentials.

Introduction: Despite its high prevalence and impact on health, metabolic dysfunction-associated steatotic liver disease (MASLD) is inadequately addressed in European primary care (PC), with a large proportion of cases going undiagnosed or diagnosed too late. A multi-country European re-search consortium led a project to design and evaluate a patient-centered, integrated model for MASLD screening, diagnosis and linkage to specialty care for European PC settings. Aim: Based on the lessons from this project, the latest research evidence and existing guidelines for the management of MASLD, we sought to develop a set of practice recommendations for screening, referral and management of MASLD in PC. Methods: The Rand/UCLA modified Delphi panel method, with two rounds, was used to reach consensus on practice recommendations. The international panel consisted of experts from six countries, representing family medicine, gastroenterology, hepatology, cardiology and public health. Initially, fifteen statements were drafted based on a synthesis of evidence from the literature and earlier findings from our consortium. Prior to the consensus meeting, the statements were rated by the experts in a first round. Then, in a hybrid meeting, the experts discussed findings of round one, adjusted the statements and reassessed the updated recommendations in a second round. Results: In round one, there was already a high level of consensus on 10 out of 15 statements. After round 2, there were fourteen statements with a high agreement (>90%). One statement was not endorsed. The approved recommendations addressed the following practice areas: risk screening and diagnosis, management of MASLD – Lifestyle interventions, pharmacological treatment of MASLD/MASH, pharmacological treatment for co-morbidity, integrated care, surgical management and other referrals to specialists. Conclusion: The final set of 14 recommendations focuses on increasing comprehensive care for MASLD in PC. The recommendations provide practical evidence-based guidance tailored to PC practitioners. We expect that these recommendations will contribute to the ongoing discussion on systematic approaches to tackle MASLD and support European PC providers by integrating the latest evidence into practice.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

Verticillium wilt is a soil borne disease caused by distinct vegetative compatibility groups (VCG) of the fungus Verticillium dahliae. Two V. dahliae isolates were recovered from symptomatic cot-ton plants in Australian cotton fields and were assigned to two distinct vegetative compatibility groups (VCGs). One corresponding to the defoliating (VCG 1A) and the other non-defoliating (VCG 2A) pathotypes of Verticillium, have been transformed with Red and Green Fluorescent protein genes, respectively. The transformants maintained their ability to infect cotton and both strains were observed to colonise the xylem vessels of cotton plants. Moreover, we observed that the cotton V. dahliae strains could also infect some sampled non-Gossypium species found in the Australian landscape. The fluorescently labelled strains of V. dahliae will allow us to gain a thorough understanding of the infection processes of this important pathogen.

To estimate the progressive collapse resistance capacity of a multi-column frame tube structure with the assembled truss beam composite floor (ATBCF), the pushdown analysis, and the nonlinear dynamic analysis as well, are conducted for such a structure by using the alternate load path (ALP) method. The bearing capacities of the remaining structures at three different work conditions, which are the side middle column failure, the edge middle column failure, and the corner column failure, are individually studied, and the collapse mechanism for the remaining structures is analyzed from the aspects of the internal force redistribution and the failure mode of the second defense line. Simultaneously, the influence of the column failure time on the dynamic response of the remaining structure and the dynamic amplification coefficient are discussed. The results show that the residual bearing capacity of the remaining structure with the bottom corner column failure is higher than that of the one with the side or edge middle column failure, while the latter has a stronger plastic deformation capacity. When the ALP method is adopted to operate the progressive collapse analysis, it is reasonable to take the column failure time as 0.1 times of the first-order vertical vibration period of the remaining structure, and it is suitable to set the dynamic amplification coefficient as of 2.0, which is the ratio of the maximum dynamic displacement to the static displacement of the remaining structure under the transient loading condition.

Accurate clinical diagnosis of patients presenting to primary care settings with acute sore throat remains challenging, often resulting in the over-prescribing of antibiotics. Using point-of-care tests (POCTs) to differentiate between respiratory infections is well-accepted, yet evidence on the application within primary care is sparse. We assessed the application of testing patients (n=160) from three family practices with suspected Streptococcal infections using rapid molecular tests (ID NOW Strep A2, Abbott). In addition to comparing clinical evaluation and prescription rates with either usual care or with testing, patients and staff completed a questionnaire about their experience of molecular POCT in primary care. The immediate availability of the result was important to patients (100%) and staff (≈90%) stated that molecular testing improved quality of care. Interestingly, only 22.73% of patients with a Centor score >2 tested positive for Strep A and overall, less than 50% of Centor scores 3 and 4 tested positive for Strep A with the ID NOW testing platform. The addition of rapid molecular POCTs to clinical assessment resulted in a 55- 65% reduction in immediate and deferred antibiotic prescriptions. The intervention was popular with patients and medical staff but was associated with increased cost and a longer appointment length.

Soil extracellular enzyme activity (EEAs) and enzymatic stoichiometry (ES) can provide a crucial indication of changes in soil ecosystem's nutrient availability and the microbial resource limitations. However, the changing characteristics of soil EEAs and ES at different stages of the native succession process and their key drivers are unclear. In order to investigate the soil EEAs, ES and driving factors of soil under vegetation at different succession stages, we adopted the "spatio-temporal substitution" method to collect the surface soil of bryophyte community, herbaceous community, shrub community and tree community in the new volcanic lava platform of Wudalianchi Volcanic Nature Reserve. We measured seven soil EEA, including carbon(C)-acquiring enzyme (β-1,4-glucosidase (BG)), N-acquiring enzymes (β-N-acetyl-glucosaminidase (NAG) and leucine aminopeptidase (LAP)) and phosphorus (P)-acquiring enzyme (acid phosphatase (AP)) activities. The length and angle of vectors defined by ratios of enzyme activities (BG/(NAG + LAP) vs. BG/AP) were used to indicate relative microbial investments in C- (length), and N- and P- (angle) acquiring enzymes. Our results showed that the contents of TC, TN, TP, MBC, DOC and NO3-N in shrub community soil were significantly higher than those in bryophyte, herb and tree communities, and increased by 441%, 246%, 137%, 5570%, 12% and 484%, respectively. The highest soil EEA of C-, N- and P-acquiring were found in shrub community, and the soil EEAs/MBC of C-, N- and P-acquiring were the highest in bryophyte community. Enzyme C:N, C:P and N:P ratios increased progressively in the order of bryophyte, herb and shrub community, but the enzyme C:N, C:P and N:P ratios of tree community were both far less than shrub community. Vector lengths increased progressively in the order of bryophyte (1.16), herb (1.27), tree (1.29) and shrub (1.40), and Vector angles decreased progressively in the order of bryophyte (49.15°), herb (45.65°), Tree (45.31°) and shurb (44.54°), suggested that as succession progresses, soil microbial nutrients transforms from P limitation (angle＞45°) to N limitation (angle＜45°). Redundancy analysis showed that TC, TN, EC and C:N were important drivers of variation in soil EEAs and ES in vegetation at different succession stages. Our findings highlight that the primary succession process cause nutrient limitation transformation. Soil ES might be a sensitive indicator mediated by soil microorganisms to the relative resource limitation at different stages of the primary succession process.

The acoustic environment in learning spaces significantly influences learning effectiveness and occupant well-being. Recent studies have shown that a series of architectural factors within physical learning environments can impact students' educational experiences. This research delves into the relationship between architectural characteristics and the perceived acoustic environment among 467 primary students in 19 learning spaces across 9 schools in Chile. The survey comprises a student questionnaire, a checklist evaluating space characteristics, and acoustic measurements of indoor noise levels during occupied conditions. Examined topics include Indoor Environmental Quality (IEQ) comfort perception, noise annoyance, hearing ability, and acoustic preference. Architectural characteristics considered encompass flexible and acoustic space design parameters. The results indicated that noise discomfort was a common issue, especially in traditional learning spaces without acoustic treatment. The type of learning space (traditional or flexible settings) has a greater impact on acoustic perception particularly concerning noise discomfort and acoustic preference. However, poorly acoustic spaces lacking absorbing materials or exhibiting lower spatial density (m2 per student) contribute to increased indoor noise levels affecting noise annoyance caused by children's talking inside. The study emphasizes the importance of considering both architectural design and acoustic conditioning for optimizing the acoustic experience in educational spaces.

Uveal melanoma (UM) poses a significant clinical challenge due to its high metastasis rate and poor prognosis. Melatonin, noted for its anti-cancer properties in various malignancies, including cutaneous melanoma, shows promise in UM treatment. This study aimed to evaluate melatonin receptor expression in primary UM and its association with UM-related mortality and prognostic factors. Immunohistochemical analysis of 47 primary UM tissues showed low expression of MTNR1A and MTNR1B receptors, with MTNR1A significantly higher in patients who succumbed to UM. Analysis of TCGA data from 80 UM patients revealed RNA expression for MTNR1A, RORα, and NQO2, but not MTNR1B or GPR50. Higher MTNR1A RNA levels were observed in patients with a BAP1 mutation, and higher NQO2 RNA levels were noted in patients with the epithelioid tumor cell type. However, Kaplan-Meier analysis did not show distinct survival probabilities based on receptor expression. The study concludes that UM clinical samples express melatonin receptors, suggesting a potential mechanism for melatonin's anti-cancer effects. Despite finding higher MTNR1A expression in patients who died of UM, no survival curve differences were observed. Further research is needed to explore additional mechanisms of melatonin’s oncostatic effects, including its antioxidant properties and immune modulation.

This study develops a progressive optimal fault-tolerant control method based on insufficient fault information. By combining passive and active fault-tolerant control manners during the process of fault diagnosis, insufficient fault information is fully used, and optimal fault-tolerant control effect is achieved. In addition, the fault-tolerant control method based on guaranteed robust cost control is introduced. The proposed progressive optimal fault-tolerant control method considers two aspects. First, as the amount of fault information continually increases, the performance index of the progressive optimal fault-tolerant controller improves. Second, at each moment, based on the corresponding insufficient fault information and prior knowledge, optimal fault-tolerant control is achieved according to current fault information. The process of progressive optimal fault-tolerant control converges to active fault-tolerant control when the fault is completely identified and the optimal fault-tolerant controller is no longer reconfigured until no more useful fault information can be provided. Furthermore, a progressive optimal fault-tolerant control algorithm based on the grid segmentation in the parameter uncertainty domain and the selection of different auxiliary center points is introduced. The simulation results verify the feasibility of the proposed algorithm and the validity of the proposed theory.

Studies on evolution have made significant progress in multiple disciplines, but evolutionary theories remain scattered and controversial. Here we deduce that, thermodynamically, many carbon-based entities (CBEs) on the Earth tend to absorb energy from widespread relatively temperate heat streams on the Earth flowing from the solar, geothermal, and other energy sources, to form higher-hierarchy CBEs (HHCBEs). This has been the driving force of evolution leading to accumulation of HHCBEs for billions of years. We further deduce three progressive mechanisms of evolution including natural selection from the driving force. We hence establish the CBE evolutionary theory (CBEET) which reinterprets the major aspects of evolution in a comprehensive and comprehensible way. The CBEET provides novel explanations for natural selection, origin of life (abiogenesis), macroevolution, sympatric speciation, and evolutionary tempos. It suggests that evolution is driven hierarchy-wise by thermodynamics and favors fitness and diversity. It elucidates that altruism, collaboration, and obeying rules with balanced freedom are important throughout the CBE evolution which includes chemical evolution, biological evolution, and animal group evolution. The CBEET refutes several erroneous views including negative entropy and survival of the fittest. It integrates with research advances in multiple disciplines and links up laws of physics, evolution in biology, and harmonious development of human society.

Resection of malignant lesions in the oral and maxillofacial area causes functional and morphological defects. To recover from these defects, reconstruction surgery is needed such as a primary closure or a flap. There are advantages and disadvantages to the method of using the primary closure and the flap, and the choice of procedure is entirely up to a surgeon. The purpose of this study is to evaluate availability of primary closure in patients. For 10 years from January 2010 to May 2020, patients who recovered using flaps after removing malignant lesions from the oral cavity and those who closed the lesion using primary closure were investigated. The investigation was conducted by searching the database of the hospital. There were 85 patients who removed malignant lesions in the oral and maxillofacial area, and among them 16 patients closed the soft tissue defects using primary closure. Operation time, histologic types, stages, wound status, and period of hospitalization according to the patients' medical records were investigated retrospectively. Between the staging and the primary closure, statistically significant differences were observed between stage I and stage II patients in 13 patients using the primary closure. (P=0.046). Statistically significant differences were identified between operation time and primary closure, with an average of 4.02 hours (P=0.015). The average period of hospitality for patients who underwent primary closure was 13.4 days, compared to 26.7 days for those who underwent flap surgery. This difference was statistically significant (P=0.0003). This study evaluated the use of primary closure in patients who underwent resection of malignant lesions in the oral and maxillofacial area. Although the majority of patients underwent reconstruction with flaps, our results showed that primary closure can be a viable option for certain patients with early-stage lesions. Therefore, oral and maxillofacial surgeons should carefully consider various evaluation criteria and select appropriate reconstruction methods to optimize functional and aesthetic outcomes for each patient.

Seventy-seven percent of Irish primary school children do not meet recommended physical activity (PA) guidelines [1]. The Daily Mile (TDM) is a primary school initiative designed to increase children’s PA output. This study evaluates TDM’s perceived effect on Irish primary school children’s health-related metrics. A mixed-methods study, comprising two data collection phases, used the RE-AIM framework to evaluate TDM [2]. Phase one involved teachers, principals and classroom assistants (n = 191) from TDM-registered schools completing a questionnaire. Two TDM-registered schools participated in phase two where, (i) interviews were conducted with each principal, (ii) a teacher sub-sample (n = 4) participated in a focus group and (iii) a child sub-sample (n = 14) participated in separate focus groups. TDM was perceived to positively impact markers of children’s health, including their PA behaviour, physical fitness and social wellbeing. Inclement weather (66.5%) and a lack of time (56.5%) were reported as the top-ranked implementation barriers. Moreover, TDM’s repetitive nature often left children feeling disinterested and resulted in some teachers modifying the initiative to maintain engagement levels. Maintaining the long-term implementation of TDM and its health benefits in primary schools may require bespoke amendments to the original format to preserve children’s engagement.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

Purpose: To assess clinical outcomes of corneal cross-linking (CXL) intervention in a population diagnosed with progressive keratoconus. Methods: This single-center retrospective cohort study included consecutive patients who underwent standard CXL or accelerated CXL for progressive keratoconus at a major teaching hospital in south Israel between January 2015 and December 2019. Patient medical files were reviewed to extract demographic, clinical, and tomographic data from outpatient clinic reports before treatment and one year post-operatively. Results: This study included 166 patients (representing 198 eyes), out of which 98 patients (123 eyes) were ethnically Bedouin, and 68 patients (75 eyes) were ethnically Jewish. Overall, 126 patients (144 eyes) had a follow-up of at least 12 months (16.84±5.76). The mean patient age was 20.62 ± 7.1 years old. There were significant baseline differences between the two ethnical groups in best-corrected visual acuity (BCVA; p < 0.001), uncorrected visual acuity (UCVA; p < 0.001), mean keratometry (p = 0.028), and corneal thickness (p < 0.001). Significant changes in BCVA, UCVA, and pachymetry parameters within each group were found after 12 months. Negative binomial regression analysis showed a maximal keratometry below 55D (RR=1.247, p < 0.001) and a standard CXL procedure (RR=1.147, p = 0.041) are significantly related to the stability of KC after 12 months. However, the effect size of the origin of patients is negligible (RR=1.047, p = 0.47). Conclusions: In this study, the Bedouin population suffered from more progressive keratoconus when compared to the Jewish population. CXL was significantly effective in improving BCVA and UCVA in both groups after 12 months of follow-up.

Progressive supranuclear palsy (PSP) is a sporadic parkinsonism tauopathy characterised by the deposition of aggregations of abnormal, hyperphosphorylated four-repeat tau (4R-tau). A revised clinical diagnostic criterion for PSP allows early presentations for the full spectrum of clinical phenotypes to be recognised enabling doctors to make a more accurate diagnosis. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT). Research into the biochemical and pathological pathways of tau is vital to improve the chances of developing an effective diagnostic biomarker to monitor tau pathogenesis. Neuroimaging biomarkers, such as tau PET ligands, are proving the most successful tool in providing a differential diagnosis between neurodegenerative disorders. There are currently no effective treatments for PSP, however tau-directed therapies in the last five years have rapidly advanced. Latest tau therapies are proposed to have disease-modifying effects by reducing toxic aggregations of tau through manipulating tau gene expression. After encouraging results from long awaited trials, additional funding is being injected into this field and with new results expected, this proves an exciting area for scientific discovery. This paper reviews advances in pathophysiology, diagnosis, biomarkers and disease-modifying therapeutic treatments for PSP.

The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. In March 2020, the World Health Organization (WHO) declared a worldwide COVID-19 pandemic. Since then, there has been a rush to find preventative or curative treatment. This arrived with the appearance of the COVID-19 vaccine, months after the declaration of the pandemic. In the setting of global COVID-19 immunization, there have been reports of rare skin immune-mediated diseases (IMD) after COVID-19 vaccination, particularly systemic sclerosis. Systemic sclerosis (SSc) is the most reported new onset IMD following messenger RNA (mRNA) COVID-19 vaccination. The pathogenesis of SSc is not fully understood, and the diagnosis is based on clinical symptoms. We report a 54-year-old male, with no prior history of autoimmune disorder, with rapid and progressive skin thickening (Modified Rodnan skin score 30/51), weeks after his mRNA COVID-19 vaccination. Antinuclear antibodies (ANA) showed a strongly positive nuclear fine-speckled pattern, but no SSc autoantibodies were found. The patient was diagnosed with SSc based on the persistence of autoantibodies and the clinical criteria according to the 2013 American College of Rheumatology/European League Against Rheumatism classification. Due to the proximity of the two events, we hypothesized a cross-reaction between COVID-19 vaccination and, in genetically predisposed patients, an emergence of systemic sclerosis. Our case suggests a potential relationship between the mRNA COVID-19 vaccine and new-onset autoimmune diseases. Physicians should be aware of this possible association.

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in 70% of Puerto Rican patients, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the framework for PCD evaluation and diagnosis, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

Graves' disease (GD) is an autoimmune disorder in which Thyrotropin Receptor Antibodies (TRAb) continuously stimulate thyroid receptors, leading to excessive production of thyroid hormones. TRAb also affect the orbital tissues, causing Graves' ophthalmopathy. Treatment to control Graves' disease consists of antithyroid drugs, radioiodine and thyroidectomy, and through such treatments, TRAb is reduced and the disease is alleviated. The mechanism by which TRAb, which play a critical role in the pathogenesis of Graves’ disease, decreases after GD treatment is still unknown. This paper presents a theoretical mechanism of how GD patients maintain a vicious cycle and how GD treatment can reduce the TRAb levels and breaks the cycle using stress-based ideas.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by alterations in motile cilia func-tion. The diagnosis of PCD is challenging due to the lack of standardized methods in clinical practice. High-speed video microscopy analysis (HSVA) directly evaluates ciliary beat frequency (CBF) in PCD. Recently, open-source ciliary analysis software applications have shown promise in measuring CBF accurately. How-ever, there is limited knowledge about the performance of different software applications, creating a gap in understanding their comparative effectiveness in measuring CBF in PCD. We compared two open-source software applications, CiliarMove and Cilialyzer, against the manual count method. We used videos rec-orded at high-speed of nasal ciliary brush samples from PCD patients and healthy controls. All three meth-ods showed lower median CBF values in PCD patients than healthy controls. CiliarMove and Cilialyzer identified lower CBF in PCD patients, similar to the manual count. Cilialyzer, CiliarMove and manual count demonstrated statistical significance (p-value < 0.0001) in the difference of median CBF values be-tween PCD and healthy controls. These findings support the utility of open-source software-based analysis tools. Further studies are needed to validate these findings with other genetic variants and identify the op-timal software for accurate CBF measurement in PCD.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

Viviparity is made possible by the placenta, a structure acquired relatively recently in the evolutionary history of eutherian mammals. Compared to oviparity, it increases the survival rate of the fetus, owing to the eutherian placenta. Questions such as “How was the placenta acquired?” and “Why is there diversity in placental morphology among mammalian species?” remain largely unsolved. Our present understanding of the molecules regulating placental development remains unclear, owing in no small part to the persistent obscurity surrounding the molecular mechanisms underlying placental acquisition. Many genes that characterize eutherian placental morphology likely evolved to be expressed at the fetal-maternal interface concurrently with those during embryogenesis. Therefore, identifying these genes, how they were acquired, and how they came to be expressed specifically at the fetal-maternal interface will shed light on some crucial molecular mechanisms underlying placental evolution. Exhaustive studies support the hypothesis that endogenous retroviruses (ERVs) could be evolutional driving forces for trophoblast cell fusion and placental structure in mammalian placentas including those of the bovine species. This review focuses on bovine ERVs (BERVs) and their expression and function in the placenta.

Noninvasive brain stimulation technique can be used for modulation of motor behaviors such as reaction time (RT). The main aim of this study was to investigate whether RT during a sequential visual isometric pinch task (SVIPT) can be affected by anodal transcranial direct current stimulation (a-tDCS) over three different stimulation sites such as dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1) or posterior parietal cortex (PPC). We also aimed to assess if stimulation of these cortical sites affect the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: 1) left M1, 2) left DLPFC, 3) left PPC and 4) sham. A-tDCS was applied concurrent with SVIPT in which the participants were precisely controlled their forces to reach seven different target forces from 10 to 40% of maximum voluntary contraction (MVC) presenting on a computer screen with right dominant hand. Four test blocks were randomly performed at baseline and 15 min after the intervention including sequence and random blocks with either hand. Our results showed significant differences between a-tDCS groups on ratio RT in the sequence blocks of both the right trained (P = .041) and left untrained hands (P = .023) for target forces of 15% and 30 % of MVC, respectively. In sequence blocks, M1 showed significant elongation in ratio RT for the target force of 15% and 30 % MVC compared to PPC and Sham groups in the right hand. In sequence blocks with left hand, this negative effect were found between M1-DLPFC and M1-Sham groups. In random blocks, no significant differences were found among four groups at each target forces for the left hand while there were significant differences for 15% (P =. 04) and 40% MVC (P =. 035) in the right hand. Our findings suggest that three different stimulation sites (DLPFC, M1 or PPC) were differentially affected by a single session of a-tDCS at some target forces during SVIPT. The effects of a-tDCS on ratio RT were transferred in the left untrained hand for sequence blocks but not random blocks. Further research is needed to understand fundamental aspects of these main areas of the brain on temporal processing in a precision control task such as SVIPT.

The behaviour of steel frame buildings under progressive collapse conditions depends on a combination of several parameters including the interplay between different collapse resistance mechanisms mobilized in different structural components. Previous studies have shown that the extent to which these mechanisms may contribute to progressive collapse resistance depends on the ability of the beam-column connections to undergo large inelastic deformations prior to reaching their deformation capacity limits. For this reason, and due to the important role of their flexural strength and tying capacity in the development of essential collapse resistance mechanisms, the response of beam-column connections is one of the most important features of progressive collapse performance. Based on the knowledge gained through previous studies on the mechanics of the problem, the role of the connections is critically reviewed by examining the results of several experimental studies conducted during the past decade. The factors that may adversely affect progressive collapse resistance – such as failure modes of certain connection types – are evaluated, and novel approaches of limiting these factors which are currently under development are reviewed. The assessment of these parameters leads to useful conclusions of practical significance, while highlighting the aspects of the problem that need further study and understanding.

Cardiovascular disease (CVD) and obesity are prevalent public health concerns with grave implications for morbidity and mortality, necessitating tailored interventions. This research explores the utility of fuzzy c-means clustering paired with principal component analysis (PCA) in detecting at-risk groups and personalizing health strategies for these conditions. Fuzzy c-means clustering allows for the dynamic classification of individuals into groups based on unique risk factors and intervention outcomes, while PCA aids in distilling complex data sets to uncover underlying patterns. The conjoined use of these methods has shown promise in identifying diverse risk profiles and in forecasting intervention success rates. The study acknowledges limitations, including possible biases stemming from data set composition and analytical parameter selection. Future research aims to refine these tools for clinical application. The results support implementing fuzzy c-means clustering and PCA for delineating specific target populations for health interventions, emphasizing careful use of these analytical approaches. Subsequent studies should focus on correlating these techniques with concrete clinical results to enhance public health measures.

Preterm infants have increased body adiposity at term equivalent age and risk for adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with

Fractional delay-Doppler (DD) channel estimation in Orthogonal Time Frequency Space (OTFS) systems poses a significant challenge considering the severe effects of Inter-Path Interference (IPI). To this end, several algorithms have been extensively explored in literature for accurate low-complexity channel estimation in both integer and fractional DDs scenarios. In this work, we develop a variant of the state-of-the-art Delay-Doppler Inter-Path Interference Cancellation (DDIPIC) algorithm which progressively cancels the IPI as estimates are obtained. The key advantage of the proposed approach is that it requires only a final refinement procedure reducing the complexity of the algorithm. Specifically, the time difference in latency between the proposed approach and the DDIPIC algorithm is almost proportional to the square of the number of estimated paths. Numerical results show that the proposed algorithm outperforms the other channel estimation schemes achieving lower Normalized Mean Square Error (NMSE) and Bit Error Rate (BER).

Pump Sizing is the process of dimensional matching an impeller and stator to provide a satisfactory performance test result and good service life during the operation of progressive cavity pumps. In this process, historical data analysis and dimensional monitoring are done manually, consuming a large amount of man-hours and requiring a deep knowledge of progressive cavity pump behavior. This work presents the use of complex networks in the construction of a prototype to recommend interference during the Pump Sizing process in a Progressive Cavity Pump. For this, data from different expert applications were used in addition to individual control Excel spreadsheets to build the database used in the prototype. From the pre-processed data, complex network techniques and the Betweenness Centrality metric were used to calculate the degree of importance of each order confirmation, as well as to calculate the dimensionality of the rotors. The model was evaluated using the mean squared error (MSE), obtaining a MSE of 0.28 for the cases where there were recommendations for order confirmations. Based on the results obtained, it was realized that there is a similarity with the dimensional defined by design engineers during the Pump Sizing process.

Background: We compared corneal visualization Scheimpflug technology (CST) parameters between eyes with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Methods: A retrospective analysis was done on data from 89 eyes with POAG and 83 eyes with PACG that had CST examinations. CST parameters were compared between eyes with POAG and those with PACG using a linear mixed model (LMM). Results: No differences were observed in age, central corneal thickness, intraocular pressure, or use of antiglaucoma eye drops between the two groups. Patients with PACG had a significantly shorter axial length (AL), a higher proportion of females, CST parameters, longer applanation 2 (A2) time, deeper A2 deformation amplitude, shorter peak distance (PD), longer whole eye movement, and longer whole eye movement time than patients with POAG. Highest concavity (HC) length and PD showed a significant positive correlation with AL. However, A1 length, A1 deformation amplitude, A2 time, A2 velocity, A2 length, A2 deformation amplitude, HC time, whole eye movement, and whole eye movement time were negatively correlated with AL. Conclusions: Biomechanical properties of the cornea differed between PACG and POAG. In some parts, AL differences between the POAG and PACG groups might contribute to the variation in CST parameters.

The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematous, celiac disease and Sjögren syndrome, and lymphoma has been widely demonstrated by several epidemiologic studies. By a not yet entirely elucidated mechanism, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to persistent stimulation of both of B- and T-cells, and to the onset of different types of lymphoma in such patients. Specifically, patients affected by may develop lymphomas may years after the original diagnosis. Several epidemiologic, hematologic and histological factors may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly diffuse large B-cell and extranodal marginal zone lymphomas is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma and predictive factors still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57 y.o. patient. The diagnostic work-up, including radiograms, core needle biopsy and histological examination are discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

Purpose: To report a novel application of excimer ablation for normalization of central corneal refractive irregularity, combined with higher fluence CXL in the effective management and visual rehabilitation of progressive keratoconus. Methods: 17 cases with progressive keratoconus were treated with a corneal surface excimer laser ablation normalization using the topographyguided (Contura) myopic ablation for customized corneal re-shaping using a 6mm optical zone. The epithelial removal was accounted for by adding a -2.75 diopters correction in the topographyguided normalizing surface ablation followed by, a second, wavefront-optimized hyperopic excimer treatment of + 2.75 diopters at 6mm optical zone. The 2 sequential excimer ablations were followed by the corneal crosslinking (CXL). Visual acuity, refraction, and keratoconus documentation via keratometry, topography, and pachymetry, as well as endothelial cell density were evaluated over 36 months. Results: Keratoconus stabilized in all cases. The severity of keratoconus stage by Amsler-Krumeich criteria improved for the OD from an average 2.2 to 1. Mean UDVA showed marked improvement at one-year follow-up all values in decimal: from 0.21±0.18 pre-operative to 0.51±0.25 at 12 months, with small additional improvement through the 3 years to 0.51±0.16. CDVA respectively increased from 0.55±0.11 to 0.77±0.14 at 1 year, and to 0.79±0.16 at 3 years. Mean minimal corneal thickness decreased significantly from 466.74±34.25 µm to 396.17±45.17 µm (P<.01) as recorded the first year postoperatively and then slightly increased to 405.17±32.21 µm at the 3-year follow-up. Conclusions: We introduce herein initial clinical data with the use of novel, off-label therapeutic excimer laser surface ablation application: Designed to perform both epithelial removal and anterior corneal stroma reshaping, to be combined with CXL, in order to apply the Athens Protocol CXL with US excimer laser approved specifications.

Multiple sclerosis (MS) is a heterogeneous disease of the central nervous system that is governed by neural tissue loss and dystrophy during its progressive phase, with complex reactive pathological cellular changes. The immune-mediated mechanisms that promulgate the demyelinating lesions during the relapses of acute episodes are not characteristic of chronic lesions during progressive MS. This has limited our capacity to target the disease effectively as it evolves within the central nervous system white and gray matter, thereby leaving neurologists without effective options to manage individuals as they transition to a secondary progressive phase. The current review highlights the molecular and cellular sequelae that have been identified to cooperate and/or contribute to neurodegeneration that identifies individuals with progressive forms of MS. We emphasize the need for appropriate monitoring via known and novel molecular and imaging biomarkers that can accurately detect and predict progression for the purposes of newly designed clinical trials that may demonstrate efficacy of neuroprotection and potentially neurorepair. To achieve neurorepair, we focus on the modifications required in the reactive cellular and extracellular milieu, in order to enable endogenous cell growth as well as transplanted cells that can integrate and/or renew the degenerative MS plaque.

The contribution deals with the selection of progressive methods and technologies to improve the management of production processes in the industrial area. The first chapter of the contribution summarises the theoretical starting points for the management of production processes and their progressive concepts. Chapter 2 deals with the analysis of the current state of play in the use of methods and technologies in production management and summarise its problem areas. Chapter 3 presents the design of a system for selecting the appropriate method and technology to improve the management of the production process. The system presented is designed from data collection blocks, a benchmark for the performance of industrial enterprises' production processes, and data mining to gain knowledge of the impact of the methods and technologies used on the performance of production processes. The last block of the system allows the presentation of the obtained results, which sets out the recommendation for the choice of progressive method and technology. The system is partially verified in the last chapter of the contribution.

: Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth and progression of ovarian tumor cells. However, no attention has been shown to their origin so far. It has been mainly assumed that CAFs in primary OC arise from the activation of resident fibroblasts. Here, we compare CAFs with ovarian location to CAFs found in peritoneal implants from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial-related markers. Therefore, as in peritoneal carcinomatosis, CAFs in primary ovarian carcinomas could be originated via a mesothelia-to-mesenchymal transition (MMT) process. The detection of mesothelial-derived CAFs in tumors confined to the ovary and associated biomarkers could be the key to early detection of peritoneal spread in affected patients.

The point cloud is a form of three-dimensional data that comprises various detailed features at multiple scales. Due to this characteristic and its irregularity, point cloud analysis based on deep learning is challenging. While previous works utilize the sampling-grouping operation of PointNet++ for feature description and then explore geometry by means of sophisticated feature extractors or deep networks, such operations fail to describe multi-scale features effectively. Additionally, these techniques have led to performance saturation. And it is difficult for standard MLPs to directly "mine" point cloud. To address above problems, we propose the Detail Activation (DA) module, which encodes data based on Fourier transform after sampling and grouping. We activate the channels at different frequency levels from low to high in the DA module to gradually recover finer point cloud details. As training progresses, the proposed Point-MDA can uncover local and global geometries of point cloud progressively. Our experiments show that Point-MDA achieves superior classification accuracy, outperforming PointNet++ by 3.3% and 7.9% in terms of overall accuracy on the ModelNet40 and ScanObjectNN dataset, respectively. Furthermore, it accomplishes this without employing complicated operations, while exploring the full potential of PointNet++.

Statistical management policy and system plays significant role in development of any nation as it guides the planner to analyze the gaps, design programs and allocate budget in efficient manner. Globally, design and usage of statistical management system varies relying on country specific ability and resources availability. Government of Nepal has been managing database in individual as well as thematic manner. Policy wise, thematic database is in operation based on Statistics Act 1958 and individual database is in operation based on Birth, Death and Other Personal Related Events Registration Act 1976. Though civil registration related policies have been either updated or newly formed, sectoral statistic management related policy has not been updated since its first promulgation period (1958). With no policy supporting the consolidated statistical management system, government as well as non-government agencies has been investing millions of dollars annually to collect, compile and analyze individual related data and fulfill their respective objectives. It has forced the government services and performance to be paper-based, time-consuming and tedious thus creating dis-trust among citizen each passing day. Though, formulation of legal instrument promoted digital movement and mandated shift towards e-government modality, the process has been low. Theoretically, Technology Acceptance Model (TAM) state the need of having advanced and efficient technology to be in place in current setting to improve governance, efficiency, accountability, transparency and trust. Also, the same theory state the requirement of strong willingness and motivation from the users (government, non-government and citizen) to adopt the technology based policy and system. As the integrated statistical management policy emphasizes on technology-based system or digital system, the perspectives of Technology Acceptance Model also termed as Information System Theory aid in understanding the context, conceptualizing and addressing the needs with an establishment and implementation of digital system or technology based system. This policy paper applied the Technology Acceptance Model (TAP) to examine the underlying opportunities and challenges associated with an integrated statistical management policy. With existing gaps in existing policy, system and practice alongside an overview of opportunities and challenges, this paper recommends the need of stand-alone integrated statistical management policy to consolidate sectoral as well as civil related information through single system based on recommended policy.

Micro satellites must survive severe mechanical conditions during their launch phase. Therefore, structural design requirements are imposed on the micro satellites. These requirements are the strength requirement and the stiffness requirement. Usually, the structural design of a micro satellite is performed using the internal stress analysis and the natural frequency analysis, which are based on a Finite Element Method (FEM). The validity of this structural design is evaluated through vibration tests. In an early stage of development, which has a FEM model of a satellite in the process of creation, presumption of the natural frequency of a satellite may be difficult. In this study, a simple method for determining the longitudinal and lateral minimum natural frequencies of the micro satellites during the ascent phase was clarified. The structure of the micro satellites used in this research is made of aluminum alloy, and they have a monocoque structure. The Young's modulus and moment of inertia of area used to calculate the minimum natural frequencies were determined using the area ratio of the monocoque structure to the entire satellite. When this method is used, the estimated minimum natural frequencies of the longitudinal direction and the lateral direction are in agreement with the measured values acquired by the vibration tests. In order to shorten the process of micro satellites development, this paper describes a practical estimation method of the minimum natural frequency for micro satellites.

Anxiety disorders, characterized by excessive fear and anxiety, are increasingly recognized as significant comorbidities in chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD). This study aimed to evaluate the prevalence of anxiety in COPD patients referred from primary care centers to pulmonology services and identify predictive factors for anxiety. Conducted as a multicentric, observational, and prospective study, 293 COPD patients were recruited, undergoing comprehensive respiratory and smoking histories, spirometry, and anxiety assessments using the Hospital Anxiety and Depression Scale (HADS). These results show: a diagnosis of suspected anxiety in in 85 patients (29.0%): 17 possible and 68 with a strong suspicion. The study found significant associations between anxiety and factors such as gender (women showed a risk 3.5 times higher than men), weight, and body mass index (BMI). Disease severity, smoking status, and clinical manifestations did not significantly influence anxiety prevalence. The findings underscore the need for systematic psychological evaluations in COPD management, advocating for the use of simple diagnostic tools like the HADS to facilitate referrals to mental health services. Addressing anxiety in COPD patients could potentially improve their quality of life and disease outcomes. The study highlights the importance of a multidisciplinary approach involving family medicine, pulmonology, and psychiatry to optimize COPD patient care and suggests future research should focus on the impact of anxiety treatment on COPD progression. These insights call for integrating psychological assessments into routine clinical practice for comprehensive COPD management.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

Rapidly progressive glomerulonephritis, the term coined for a subtype of nephritic syndrome, is characterized by a state of acute loss of renal function, along with those components of renal damage on urinalysis, over a relatively short period (a few weeks or months). It is the aftermath of an acute, severe glomerular injury. RPGN, famously known as Crescentic glomerulonephritis (cGN) is not a single disease entity but a pattern that can occur in a variety of glomerular diseases caused by different pathologic lesions leading to the development of necrosis in the glomerular capillaries seen in both, systemic and kidney-restricted diseases. While still little is known about the exact etiologic cause behind the primary injury to the capillary wall leading to the development of the condition, many mechanisms are put forth to describe the pathogenesis leading to the progression. Immunopathologic studies have demonstrated that rapidly progressive glomerulonephritis can result from glomerular antibody deposition, can be immune complex-mediated, or from some as yet undefined mechanism that doesn’t involve glomerular antibody deposition. The condition is often severe with poor prognosis as it develops so rapidly and with extensive glomerular involvement, the damage is almost irreversible. Many elements can be associated with the occurrence and progression of the disease but it often involves a disruptive immune response one way or the other. RPGN’s morphological hallmark, the extensive extra-capillary cellular proliferation into the bowman’s space, commonly known as crescent formation which is often observed by electron microscopic view of the tissue biopsy, is considered one of the great diagnostic approaches for the detection of the disease. Also, the severity of the disease is related to the nature and type of immunologic process causing the disease and (in part) to the degree of crescent formation, that can only be observed by histopathological studies. This activity attempts to explain the etiology and pathogenesis involved in the development leading to the rapid progression of the disease.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

Transmission of values and religious concepts to children is one of the most important issues in the third millennium and it has drawn varied and different views among experts and scholars in the world. Research specialized in religious literature for children and adolescents create new capacities in the presentation of religious concepts to the group. Plans have been considered to transfer values and religious concepts in the curricula of primary school children in the group in Iran. It is one of the topics that the authors note to the introduction of the minutiae of religion in the first three elementary grades. In this study, the collection and analysis methods providing content related to the minutiae of religion in reading books the first till third sections of the years 2013-2015. In addition, the plan includes aspects of other branches of religion in these books on information collected from text books that collected and classified. The result is that "definitely good and forbidding the evil" and "prayer" have the highest frequency of applications in the selected books. Further branches made of branches of religion in these books, represents the values of religious, moral and social as well.

Background. Primary Stabbing Headache (PSH) is characterized by brief, focal and paroxysmal pain (“stab”), occurring sporadically or in clusters. Data on pediatric cases are poor. Methods. We performed a comprehensive literature review searching Pubmed, Cochrane and Embase in order to collect pediatric case reports and case series of PSH. Results. Twelve out of 162 articles assessed for eligibility were finally included. Prevalence of PSH and probable PSH varies from 2.5 to 10% among children with primary headaches and it is higher among children aged less than 6 years old. The mean age of onset is between 7 and 11 years of age. Attack duration greatly varies, ranging from a few seconds to several minutes. Intensity of pain is usually from moderate to severe. Associated symptoms are infrequent but may be observed (mainly photophobia, vertigo, nausea and vomiting). Neuroradiological findings are usually unremarkable; EEG may show sporadic epileptiform abnormalities (up to 30% of cases). Preventive therapy is anecdotal, including treatment with indomethacin, trazodone, valproate and amitriptyline. Conclusion: PSH is a common but still underdiagnosed entity among children with primary headache; further and larger cohort studies are needed to better assess, in particular, prognosis and response to therapy.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p

Mesoscale eddies wield a significant influence on primary productivity in marine ecosystems by regulating nutrient availability, vertical mixing, and phytoplankton growth dynamics. In this study, we tracked and analyzed the effects of mesoscale eddies on net primary productivity (NPP) across the Bay of Bengal (BoB) using remote sensing data. Dividing the Bay into six zones based on mesoscale eddy frequency and distribution, our analysis identified 1880 anticyclonic eddies and 1972 cyclonic eddies during January 2010–March 2020 monitoring period. Cyclonic eddies predominantly occurred in the western part of the bay - along the east coast of the Indian Peninsula; while anticyclonic eddies were also observed, albeit in lesser proportions. Among eddies lasting one-week, anticyclonic eddies comprised approximately 48.81%, while cyclonic eddies constituted approximately 51.19% of the total. Analysis of the NPP distribution across the months revealed intriguing patterns. Mean values of NPP fluctuated throughout the year, with the highest value observed in August (748.51 mg C/m2/day) and the lowest in May (519.26 mg C/m2/day). The findings indicate a complex relationship between eddy distribution and NPP, with Zones 1 and 2 exhibiting a higher occurrence of cyclonic eddies, correlating with greater NPP and its variability. Conversely, Zones 3 and 5 display increased eddy activity despite fewer cyclonic eddies and lower NPP levels. Zone 6 shows reduced eddy activity and NPP, while Zone 4 presents moderate eddy activity alongside lower NPP. In contrast, Zones 3 to 5 exhibit lower NPP levels despite exhibiting heightened eddy activity. This study contributes valuable insights into the dynamics of ocean circulation and the impacts of eddies on NPP, which can inform fisheries management strategies, advances climate resilience measures, expands scientific knowledge, and guides policies related to conservation and sustainable resource utilization.

The rampant misuse of drones poses a serious threat to national security and human life. Currently, the CNN method has been widely used in drone detection. However, there is a challenge that traditional CNN cannot cope with, which is small drone targets often have reduced amplitude or even lost features in infrared images. This paper proposes a Progressive Feature Fusion Network (PFFNet) that gradually increases the response amplitude of the target in the deep network. The Feature Selection Model (FSM) is designed to improve the utilisation of the output coding graph and enhance the feature representation of the target in the network. A lightweight segmentation head is also designed to achieve progressive feature fusion with multi-layer outputs. Experimental results show that the proposed algorithm can achieve low duration and high accuracy in drone target detection. On the public dataset, the IoU is improved by 2.53% and the detection time is reduced by 81.03%.

A progressive FEA fatigue degradation model for composites was developed and implemented using a UMAT user material subroutine in Abaqus. Numerical results were compared to experimental strain field data from high frequency Digital Image Correlation (DIC) of split disk fatigue testing of pressure vessel cut outs with holes. The model correctly predicted the onset and evolution of damage in the matrix as well as the onset of fiber failure. The model use progressive failure analysis based on the maximum strain failure criterion, the cycle jump method and Miner sum damage accumulation rule. A parameter study on matrix properties was needed to capture the scatter in strain fields observed experimentally by DIC. S-N curve for the matrix material had to be lowered by 0% to 60% to capture the experimental scatter. The onset of local fiber failure had to be described by local S-N curves measured by DIC having 2.5 times greater strain than that of S-N curves found from standard coupon testing.

Atomic force microscopy (AFM) has been extensively used for the nanoscale characterization of polymeric materials. The coupling of AFM with infrared spectroscope (AFM-IR) provides another advantage to the chemical analyses and thus helps to shed light upon the study of polymers. In this perspective paper, we review recent progress in the use of AFM-IR in polymer science. We describe first the principle of AFM-IR and the recent improvements to enhance its resolution. We discuss then the last progress in the use of AFM-IR as a super-resolution correlated scanned-probe IR spectroscopy for chemical characterization of polymer materials dealing with polymer composites, polymer blends, multilayers and biopolymers. To highlight the advantages of AFM-IR, we report here several results in studying crystallization of both miscible and immiscible blends as well as polymer aging. Then, we demonstrate how this novel technique can be used to determine phase separation, spherulitic structure and crystallization mechanisms at the nanoscale, which have never been achieved before. The review also discusses future trends in the use of AFM-IR in polymer materials, especially in polymer thin film investigation.

The global issues of overweight and sedentary lifestyles demand comprehensive responses from health systems, yet health education still needs to be more cohesive and less sporadic. This study focuses on primary school children as a specific target for instilling healthy habits, employing ac-tive learning strategies to address healthy diet and physical activity. Through Problem-Based Learning projects, the study engaged fourth-grade primary students in acquiring healthy habits. The study was carried out over four consecutive years at a school with two lines, allowing the employment of an opportunity sample and evaluating intervention and control groups by com-paring their corresponding scores. Control groups integrated a total of 54 students, while the in-tervention group included a total of 159 students. A pre-test and post-test questionnaire were used for data collection. Evaluation differential scores revealed statistically significant higher scores in the intervention groups: 3.62 points in control groups and 6,94 in intervention groups, particu-larly in attitudinal competences. These strategies not only facilitated the development of crucial skills such as information search, synthesis, representation, analysis, decision-making, teamwork, and intrapersonal awareness but also significantly broadened the knowledge acquired in aspects related to healthy habits. This approach proved effective in helping children comprehend the im-portance of healthy choices and encouraged integrating such habits into their daily lives.

The objective of this study is to analyze the assessment practices in primary education and how they relate to the valuation of the learning process. It seeks to understand the perceptions of teachers and students regarding assessment and to observe classroom activities, as well as to analyze the assessment instruments used. The method used is a mixed approach that combines qualitative interpretations of the participants’ realities with a phenomenological analysis to reflect on the evaluative practices. The results indicate a contradiction between what is said and what is done in terms of evaluation, with a tendency to use written tests and traditional exams instead of a combination of techniques that allow for a significant evaluation of student learning. In addition, significant differences are observed among teachers regarding the importance they give to evaluation within their practices and evaluative models.

Background: Primary lymphedema is a chronic condition caused by a developmental abnormality of the lymphatic system and its malfunction. Different surgical options such as physiologic and excisional procedures have been proposed. The aim of this study was to present a complete algorithm for the treatment of primary lower extremity lymphedema: Primary LYmphedema Multidisciplinary Approach (P-LYMA). Methods: Nineteen patients were treated according to the P-LYMA. Patients underwent pre- and post-operative complex decongestive therapy (CDT). Different physiologic and excisional procedures were performed independently or in combination. The primary outcome was the circumferential reduction rate (CRR). The Lymphedema Quality of Life Score (LeQOLiS), reduction in the number of episodes of cellulitis, length of stay, and complications were recorded. Results: The mean CRR calculated was 72.8±19.6% after twelve months. The episodes of cellulitis per year decreased from a mean of 1.9±0.8 preoperative to 0.4± 0.6 throughtout follow-up. Two patients experienced minor complications. Mean hospitalization time was 5 days. Patients’ quality of life (LeQOLi score) drastically improved from 70.4±11.6 to 24.2 ±13.9 at twelve months post-op. Conclusion: The P-LYMA algorithm allows to maximize surgical results and improve the quality-of life in patients who suffer from primary lymphedema. CDT is mandatory to optimize results.

This paper examines the most prominent “progressive” American religious groups’ (as defined by those that liberalized early on the issue of birth control, circa 1930) views of women between the first and second waves of the feminist movement (1930-1965). We find that some groups have indeed had a long and outspoken support for women’s equality. Using their modern-day names, these groups, the United Church of Christ, the Unitarian Universalist Church, and to a lesser extent, the Society of Friends, or Quakers, professed strong support for women’s issues, early, and often. However, we also find that prominent progressive groups –the Protestant Episcopal Church, the Methodist Episcopal Church and the United Presbyterian Church, were virtually silent on the issue of women’s rights – even as the second wave of the feminist movement was picking up steam – as late as 1965.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might have reduced the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patient with diabetes and those with obesity, as well as considering sex-based differences. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to develop a personalized approach.

If we assume that: a. The four fundamental forces of nature are independent waves without rest masses, and their speeds are constant in a vacuum, just like light. b. Light or electromagnetic waves and gravity are comparable in structures. Weak and strong interactions are similar in structures. c. Light and weak interaction have the same speed c_L with spin number +1 or –1. d. Gravity and strong interaction have the same speed c_G without spin. e. The primary particles, namely electrons, electron neutrinos, and dark neutrinos in this paper, are made by the above four waves. We can find and describe some fundamental characteristics of the primary particles (e.g., their sizes, energies, and interactions) and introduce new attractive results from them (e.g., the source of the Pauli exclusion principle, the solution to the Einstein-Podolsky-Rosen paradox, and c_G slightly faster than c_L).

In zebrafish inner ear, hair cell orientation in anterior and posterior maculae of the embryonic otic vesicle is different (about 30–40 degrees): this is rather unusual in planar polarity mechanism of action, instead suggests that kinocilia may be rotationally polarized. In mice node, the innermost monociliated cells generate a left-ward fluid flow sensed by the immotile primary cilia of Left peri-nodal cells: the Nodal signaling pathway is then expressed asymmetrically, in the Left lateral plate mesoderm, breaking symmetry in visceral organs (situs solitus); however, Right peri-nodal cells also, if artificially excited by a right-ward flow, break symmetry and activate the Nodal cascade, though inverting visceral organ asymmetry (situs inversus); surprisingly, peri-nodal cells prove to be adept at distinguishing flow directionality. Recently, in the Kupffer vesicle (the zebrafish laterality organ), chiral primary cilia orientation has been described: primary cilia, in the left and right side, are symmetrically oriented, showing a mirror average divergence of about 15–20 degrees from the midline. This finding, taken together with the mirror behavior of mouse perinodal cells and zebrafish hair cells, champions the idea of primary cilia enantiomerism.

We describe a 90-year-old male presenting with disequilibrium, loss of balance and difficulty walking for three days prior to initial presentation. Interestingly, he denied cough, fever or dyspnea prior to arrival. Over the course of 48 hours, the patient developed acute respiratory distress syndrome (ARDS) requiring intubation, diagnosed with COVID-19 infection and was treated in the intensive care unit where he died. Since the initial cases in Wuhan China in Dec 2019, the medical and epidemiological communities have learned much about the presenting features, symptomatology, epidemiology, transmission and common physical, laboratory and radiological findings of this disease. Although common symptoms are already established, it is very important to learn and record atypical symptoms or presentations of this highly contagious disease. By doing so, we will be able to recognize earlier atypical symptoms and prevent the environmental exposure to Health care workers and future patients as well. We report that Central disequilibrium may be such as initial presenting sign and symptom of impending respiratory failure from SARS-CoV-2 virus. These atypical findings such as presyncope may precede common respiratory complications of SARS-CoV-2.

Abstract: Patients with Cleft Lip Palate (CLP) require comprehensive treatment, so the people who take care of them must constantly provide care and support, along with continuous care and support from their caregivers, often extending until youth. The purpose was to compare the Quality of Life (QoL) of caregivers of children with CLP with those without the condition. A cross-sectional paired study was conducted at the Dental Clinic of the Escuela Nacional de Estudios Superiores (ENES León), National Autonomous University of Mexico (UNAM), from May to December 2021. Primary caregivers of patients with CLP (n=70) were included as well as those of the patients without CLP (n=70) of the same institution. Sample size was calculated considering an OR=2.5, establishing a convenience selection. Caregivers answered the WHOQoL Bref instrument to assess QoL. Of the total sample analyzed, 88.6% of the caregivers were female (p>0.05). Caregivers of patients with CLP reported poor QoL (64.8%), compared to caregivers in the control group (p

Headache is considered to be one of the most common causes of medical treatment and evaluation worldwide in both acute and outpatient settings. It is the most common neurological symptom seen worldwide affecting all genders, ages, ethnicities, and socioeconomic levels. It’s impact is noted in educational decline in school-aged children and decreased productivity through sick leave in adults. Its overall burden is well documented in well-resourced countries but limited data is seen low resourced countries. While many underlying causes bring about secondary headaches, primary headaches and more specifically migraines have been more widely explored. Migraines have a distinct criterion that is inclusive of one day duration (4 hours to 7 days, unilateral distribution, nausea and vomiting and disability as a few examples. However, migraines can vary and proper documentation through a migraine diary can help to guide treatment. Management of migraines can vary. Lifestyle modification is a key factor in the overall prevention and reduction of triggers in migraines. In addition to this, pharmacotherapy can be given in a tier-based approach based on overall severity and frequency of the migraine. Interventions have progressed from botox injection and have seen the advent of new medications such as nasal sprays to novel formulations of pre-existing drug formulations. Nonetheless, there is great room for further studies of headaches and migraines. Research specifically in low-resource countries can prove to beneficial.

EUS–TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS–TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS–TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS–TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity ≥ 20% and tissue area ≥ 4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.

Let $G$ be a group with identity $e$ and $R$ be a commutative $G$-graded ring with nonzero unity $1$. Graded semi-primary and graded $1$-absorbing primary ideals have been investigated and examined by several authors as generalizations of graded primary ideals. However, these three concepts are different. In this article, we characterize graded rings over which every graded semi-primary ideal is graded $1$-absorbing primary and graded rings over which every graded $1$-absorbing primary ideal is graded primary.

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

Primary Biliary Cholangitis (PBC) is a chronic, cholestatic liver disease with a heterogeneous presentation, symptomatology, disease progression, and response to therapy. The current risk stratification assessment, aimed at identifying patients with a higher risk of disease progression, encompasses an in-depth analysis of demographic data, clinical and laboratory findings, antibody profiles, and the evaluation of liver fibrosis using both invasive and non-invasive techniques. Treatment response scores after one year of therapy remain to date a major factor influencing the prognosis of PBC patients. While the initial therapeutic approach with ursodeoxycholic acid (UDCA) is universally applied, new second-line treatment options have recently emerged, with many others under investigation. Consequently, the prevailing one-size-fits-all approach is poised to be supplanted by tailored strategies, ensuring high-risk patients receive the most appropriate treatment regimen from diagnosis. This will require the development of a risk prediction model to assess, at the time of diagnosis, the course, outcome, and response to first and additional treatments of PBC patients. This manuscript provides a comprehensive overview of the current and emerging tools used for risk stratification in PBC and speculates on how these developments might shape the disease landscape in the near future.

Abstract Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Because of the multiplicity of roles in cell function, it is not surprising that deficiency of CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation.

Restrictive cardiomyopathy is a rare cardiac disease causing severe diastolic dysfunction, ventricular stiffness and dilated atria. In consequence, it induces heart failure often with preserved ejection fraction and is associated with a high mortality. Since a poor clinical prognosis, patients with restrictive cardiomyopathy require frequently heart transplantation. Genetic as well as non-genetic factors contribute to restrictive cardiomyopathy and a significant portion of cases remains of unknown etiology. However, the genetic forms of restrictive cardiomyopathy and the involved molecular pathomechanisms are only partially understood. In this review, we summarize the current knowledge about primary genetic restrictive cardiomyopathy and describe its genetic landscape, which might be of interest for geneticists as well as for cardiologists.

Schiff bases attract research interest due to their applications in chemical synthesis and medicinal chemistry. In recent years, benitrobenrazide and benserazide containing imine moiety, have been synthesized and characterized as promising inhibitors of hexokinase 2 (HK2) an enzyme overexpressed in most cancer cells. Both compounds possess a common structural fragment, a 2,3,4-trihydroxybenzaldehyde moiety connected through hydrazone or hydrazine linker with acylated on N’-nitrogen atom by serine or 4-nitrobenzoic acid fragment. To avoid presence of toxicophoric nitro group in benitrobenrazide molecule we introduced common pharmacophores 4-fluorophenyl or 4-aminophenyl substituents. Modification of benserazide regards an introduction of other endogenous amino acids instead of serine. Herein we report the synthesis of benitrobenrazide and benserazide analogues and preliminary results of inhibitory activity against HK2 evoked by these structural changes. The derivatives contain a fluorine atom or amino group instead of a nitro group in BNB, exhibited the most potent inhibitory effects against HK2 at a concentration of 1 µM, with HK2 inhibition rates of 60% and 54%, respectively.

Improving the quality and access to healthcare services in rural areas is fundamental to develop sustainable healthcare systems. This research aims to explore the motivations of healthcare professionals to work and settle in rural island areas of Greece with limited access to secondary and tertiary care. The study suggests practical ways to encourage self-motivation and attract more health workers in rural areas. An exploratory qualitative research approach was employed, involving semi-structured interviews with 16 healthcare professionals working in primary care units that lack direct hospital or hospital-health center access. The research was conducted specifically in the rural islands of Cyclades. Thematic analysis was conducted to identify common themes and unique insights from the participants. The analysis revealed three thematic categories. Τhe «attraction» thematic was influenced by personal factors, random selection, origin, accommodation factors, professional factors and obligatoriness. The «recruitment» thematic was associated with understaffing, special care issues, unstable working environment, educational and organizational aspects, and insular lifestyle. The thematic of «retention» highlighted personal issues, accommodation difficulties, economic and work-related issues, and unique challenges posed by an insular lifestyle. This research provides valuable insights into the motivations that drive healthcare professionals to settle, work, and remain in remote island units, as well as the challenges they encounter in making this decision. The study proposes strategies to motivate and attract more healthcare professionals to rural areas. These findings should be considered when formulating or reviewing primary healthcare empowerment policies to ensure equitable healthcare access for all individuals.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Primary urethral malignancies are rare in clinical practice and elderly female are prone to suffer. The cause of PUC is unknown and may be related to long-term chronic inflammation, infection, sexual intercourse, pregnancy and irritation of the urethra. Incipient symptom of PUC is not distinctness and can easily lead to misdiagnosis. The final diagnosis relied on transvaginal ultrasound-guided mass biopsy and urethral biopsy. Early tumor treatment is mainly based on surgical resection. For advanced tumors, it is recommended to adopt a comprehensive treatment plan combining surgery, radiotherapy and chemotherapy We report this case with the aim of bringing attention to that primary urethral cancer progresses rapidly and has a poor prognosis, it is urged to call for a need of diagnostic and treatment specification.

Introduction: The coronary flow reserve (CFR) is a sign of early-stage coronary artery disease (CAD). Plasma atherogenic index (PAI) is related to atherosclerosis and cardiovascular mortality. Therefore, our aim was to determine CFR and PAI in patients with primary hyperparathyroidism (PHPT) and investigate whether PAI can be used in the detection of early-stage CAD. Material and Methods: The sample was comprised of 44 patients with PTHT and 33 healthy volunteers. We defined CFR as the ratio of the hyperemic diastolic peak velocity to the baseline diastolic peak velocity. PAI values were calculated with the formula of log 10 triglyceride (TRG) / high-density lipoprotein (HDL). Result: The comparison of the groups for PAI and CFR demonstrated that PAI levels were significantly higher while CFR levels were significantly lower in the PTHT patients (p<0.01, p=0.01, respectively). The correlation analysis revealed that CFR was negatively correlated with PAI and TRG (PAI- p<0.0001 r=-0.537).The multivariate logistic regression analysis showed that only a high PAI level (OR: 151.6, 95% confidence interval (CI): 4.1-5480, p=0.006) was an independent predictor of reduction in CFR in PHPT patients. Conclusion: Overall, we found an independent correlation between PAI and CFR values. Hence, PAI may be useful in identifying PHPT patients facing a high risk of adverse cardiovascular events and may also allow early diagnosis of subclinical atherosclerosis.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analysed the levels of EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express EGFR and found that EGFR-expressing cells responded to EGF ligand by increasing ODZ1 at the mRNA and protein level. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway or siRNA-mediated knockdown of MAPK11 (p38 MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signalling pathway through p38 MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

This study investigates effective strategies for second language education in primary schools, analyzing the efficacy of immersive and interactive methods, digital literacy tools, and mixed-method approaches. The findings reveal significant improvements in language proficiency and student engagement through these methodologies, with immersive and interactive strategies showing substantial benefits in oral proficiency and engagement, digital tools enhancing accessibility and engagement, and mixed-method approaches yielding the highest overall effectiveness. The study underscores the importance of a balanced, flexible approach to language education, integrating traditional and modern methods to cater to diverse learner needs. These strategies not only advance linguistic skills but also contribute to the broader cognitive and emotional development of young learners, emphasizing the critical role of effective language education in preparing students for a globalized world.

Background: Disorders of immunity are poorly recognised in some rare multisystem genetic con-ditions. We aim to describe syndromic features and immunological defects in children with syn-dromic primary immunodeficiencies (sPIDs). Methods: This is a retrospective descriptive study of children aged 0-18 years with sPIDs under the care of the paediatric immunology service at the Bristol Royal Hospital for Children, United Kingdom from January 2006 to September 2021. Results: sPIDs were identified in 36 patients. Genetic diagnoses which are not commonly associ-ated with PIDs and not included in the International Union of Immunological Societies classifica-tion were present in 7/36 (19%): Trisomy 22, Arboleda-Tham syndrome, 2p16.3 deletion syn-drome, supernumerary ring chromosome 20 syndrome, Myhre syndrome, Noonan syndrome, trichothiodystrophy/Cockayne syndrome complex. Recurrent and/or severe infections were the commonest clinical features (n=33, 92%). Approximately half had combined immunodeficiency or antibody deficiency. Commonest extra-immunological manifestations include dysmorphism (72%), disorders of nervous (78%), musculoskeletal (69%), haematology/lymphatic (58%), and gastrointestinal, hepatic/pancreatic (58%) systems. Conclusions: Patients with sPIDs often have multiorgan involvement and some are non-immunologically mediated. There should be low threshold to clinically assess and investi-gate for disorders of immunity in any patients with syndromic features especially when they pre-sent with recurrent/severe/opportunistic infections, features of immune dysregulation, autoin-flammation or lymphoproliferation.

Background: The main of this study was to realize a systematic review of clinical features and prognosis factors associated to diagnosis and prognosis of primary hyperaldosteronism in cats. Methods: Clinical cases with hyperaldosteronism confirmed with histopathological analysis have been included. Studies without information about clinical confirmation, type of carcinoma or affected system were excluded. A total of nine studies with seventeen patients with primary hyperaldosteronisms were used for this systematic review. Results: All cats included presented hypertension, renal failure (34.48%), ocular problems (27,59%), cardiovascular alterations (24.14%) and nervous system defects (13.79%). High levels of blood pressure and serum levels of aldosterone are related to adenocarcinoma, whereas the potassium levels were lower than cats with adenoma or bilateral hyperplasia. Conclusions: In primary feline hyperaldosteronism, patients with adenocarcinoma show higher levels of aldosterone, higher blood pressure and lower potassium levels than patients with adenoma or nodular hyperplasia. Adrenocortical adenocarcinomas are more frequent in older cats than young, and these patients present several clinical signs, mainly renal failure, and ocular complications. Regardless of aldosterone levels, a favorable prognosis is associated with adrenalectomy.

Monitoring photosynthesis is a great challenge to improve our knowledge of plant productivity at the ecosystem level, which may be achieved using remote-sensing techniques with synoptic abilities. The main objective of the current study is to take up this challenge for microphytobenthos (MPB) primary production in intertidal mudflats. This was achieved by coupling hyperspectral radiometry (reflectance, ρ and second derivative, δδ) and PAM-fluorometry (non-sequential light curve, NSLC) measurements. The later allowed the estimation of the primary production via the light use efficiency (LUE) and the electron transport rate (ETR) whereas ρ allowed to estimate pigment composition and optical absorption cross-section (a*). Five MPB species representative of the main growth forms: epipelic (benthic motile), epipsammic (benthic motile and non motile) and thycoplanktonic (temporarily resuspended in the water column) were lighted at increasing light intensity from dark to 1950 µmol photons.m^-2.s^-1. After spectral measurements, a* was retrieved using a radiative transfer model and several radiometric indices were tested for their capacity to predict LUE and ETR. The spectral estimation of these two photosynthetic variables was subsequently compared to the values estimated by PAM-fluorometry. Results showed that different responses related to the xanthophyll cycle (de-epoxydation state) were observed for the three growth-forms with increasing light levels. However, a single relationship with radiometric index was not affected by species/growth-forms, i.e. δδ_496/508, called the MPB_LUE index to predict LUE and ETR. This index has the potential to be applied to air borne hyperspectral imagery for large-scale assessment of MPB production.

Methotrexate (MTX) is commonly used in intrathecal chemotherapy for patients with acute lymphocytic leukemia (ALL) to prevent central nervous system (CNS) involvement. However, the use of MTX-based chemotherapy can lead to rare yet severe complications, such as MTX-induced myelopathy. Here we report the case of MTX-induced myelopathy initially misdiagnosed as Guillain-Barre syndrome, leading to a delay in diagnosis and treatment. We present a case of a 39-year-old male with a history of B-cell acute lymphoblastic leukemia (B-ALL) who experienced bilateral foot paresthesia and progressive lower extremity weakness after intrathecal methotrexate (MTX) treatment. Initially suspected as Guillain-Barre syndrome (GBS) due to similar clinical features and nerve conduction studies. The patient received intravenous immunoglobulin (IVIG) treatment, but his condition worsened. A subsequent spine MRI revealed MTX-induced myelopathy. This case highlights the diagnostic challenge posed by the similarity in clinical presentation between MTX-induced myelopathy and GBS. Differentiating between these conditions is critical for appropriate management. Prompt recognition and treatment with folate metabolism compounds may mitigate neurological sequelae.

A new layout optimization method for offshore wind farms is proposed to minimize power deficits due to wake effect. The main engine of the algorithm is a gradient-descent method, in which an analogy is established between power deficit and repulsive electrostatic potential energy. To achieve a maximum dispersion in the initial solution, throughout the optimization process, new turbines are included in the centre of the concession area, and quickly expand outward looking for areas with less potential, in turn pushing the previous ones. When the optimization process ends, to avoid local maximums, it enters into a process of suppression of the set of locations that cause the greatest potential (power deficit). Then, a potential map of the entire area is created and a greedy algorithm includes new turbines to complete the layout with the final number of turbines. To speed up the search process and the creation of the potential map, two simplifications have been validated and added: the spatial distribution of velocities has been converted into its equivalent with point symmetry; and, for turbines affected by multiple wakes, the power deficit has been calculated by using a linear aggregation of powers, instead of the usual linear (or quadratic) aggregation of speeds. Owing to this type of aggregation, the process is accelerated in a factor of 90.

Background: The current review was conducted to determine the effectiveness of atenolol on all-cause mortality rate among Asian patients with chronic progressive diseases, mainly diabetes mellitus, primary hypertension, and coronary artery disease. Methods: We searched the COCHRANE, MEDLINE, TRIP, and EMBASE databases for published articles up to 31 March 2023. Studies that compared all-cause mortality rates among Asian patients who were on atenolol or other medications were included. Results: The review included 79603 Asian patients from three cohort studies. Out of the studied patients, 36046 were atenolol users and 43557 were non-atenolol users. The review revealed that atenolol users recorded lower all-cause mortality rates compared to non-users with a significant difference (OR= 0.57, CI= 0.44-0.75, P<0.001). The pooled estimate of the all-cause mortality rate was also lower among atenolol users (7.02%) compared to metoprolol tartrate users (13.15%) with a significant difference (OR= 0.50, CI= 0.47-0.53, p < 0.0001). Although the included studies were categorized as having a low risk of bias for most of the studied domains, significant heterogeneity was recorded across these studies (I2 =88%, P=0.001). Conclusion: This review found that atenolol when compared to a control or metoprolol tartrate, has a significant effect in reducing the all-cause mortality rate among Asian patients with chronic progressive disease.

Managers are often faced with the task of improving the management of the production 17process in order to maintain the sustainability of production efficiency in a highly competitive en-18vironment. The submitted contribution deals with the design of a system that will support them in 19the selection of progressive methods and technologies in order to improve the management of pro-20duction processes. Managers often follow new trends in this issue, but it is not easy to work on the 21knowledge that proven progressive technologies can bring them higher efficiency. The presented system is based on the use of knowledge of existing solutions of manufacturers of automotive components, where companies solve similar problems in production management. The mix of methods and technologies used in the management of production processes brings companies different results in the achieved efficiency. The proposed system for supporting the selection of the production management method and technology is designed from blocks of data collection, benchmarking of the performance of production processes of industrial enterprises, and further from data mining technology to obtain knowledge about the effect on efficiency from already implemented technologies. The last blocks help to examine the differences in the implementation of the same methods and technologies and allow to present the obtained results to the manager in the form of recommendations for choosing a suitable progressive method and technology.

Background: Mosaic cancers are composed of two or several genetically different cell populations. Mosaicism has been considered to be rare among malignancies, with the exception of the germ cell tumours. Although it has been described that neuroendocrine foci might be present within adenocarcinomas of the prostate, this was meant for advanced stage diseases and the clinical relevance of the histological finding has not been clarified. Patients and methods: We recall a single centre cohort of patients with neuroendocrine cancer of the prostate. We show for the first time histological images of a primary mosaic neuroendocrine/adenocarcinoma of the prostate. Results: Contrarily to the general assumption of a rare disease with poor prognosis, the clinical incidence was found to be 2%, being 50 fold higher than the earlier data. During the follow-up the overall survival of some metastatic patients reached several years. The particularity of patients with favourable outcome was the parallel elevation of PSA and NSE. They received anticancer treatments in an alternating way directed according to the tumour marker that was actually in rise. Histological images of primary mosaic prostate cancers are shown. A model explaining the development of mosaic cancers is presented. Conclusion: Mosaic neuroendocrine-/adenocarcinoma of the prostate is underdiagnosed and its prognosis is underestimated.

Today, concepts such as Emotional Education and Emotional Intelligence are recognized by many authors and researchers, emphasizing the importance of their development in all people, but especially in schools, specifically in teachers or educators and children. However, we still find many shortcomings within the schools that are needed to continue working. The aim of this study is to investigate the presence of emotional intelligence and empathy in teachers, through a sample of 42 participants. The research was conducted based on two validated and highly reliable assessment tools, called TMMS-24 and TECA. The results of the TMMS-24 indicate that a large percentage of participants have an adequate score of emotional intelligence. The results of the TECA indicate that most of the participants are in the middle, high or extremely high scores in relation to the level of empathy.